Biology:Radioactive tracer

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Short description: Chemical compound

A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products. Radiolabeling or radiotracing is thus the radioactive form of isotopic labeling. In biological contexts, experiments that use radioisotope tracers are sometimes called radioisotope feeding experiments.

Radioisotopes of hydrogen, carbon, phosphorus, sulfur, and iodine have been used extensively to trace the path of biochemical reactions. A radioactive tracer can also be used to track the distribution of a substance within a natural system such as a cell or tissue,[1] or as a flow tracer to track fluid flow. Radioactive tracers are also used to determine the location of fractures created by hydraulic fracturing in natural gas production.[2] Radioactive tracers form the basis of a variety of imaging systems, such as, PET scans, SPECT scans and technetium scans. Radiocarbon dating uses the naturally occurring carbon-14 isotope as an isotopic label.


Isotopes of a chemical element differ only in the mass number. For example, the isotopes of hydrogen can be written as 1H, 2H and 3H, with the mass number superscripted to the left. When the atomic nucleus of an isotope is unstable, compounds containing this isotope are radioactive. Tritium is an example of a radioactive isotope.

The principle behind the use of radioactive tracers is that an atom in a chemical compound is replaced by another atom, of the same chemical element. The substituting atom, however, is a radioactive isotope. This process is often called radioactive labeling. The power of the technique is due to the fact that radioactive decay is much more energetic than chemical reactions. Therefore, the radioactive isotope can be present in low concentration and its presence detected by sensitive radiation detectors such as Geiger counters and scintillation counters. George de Hevesy won the 1943 Nobel Prize for Chemistry "for his work on the use of isotopes as tracers in the study of chemical processes".

There are two main ways in which radioactive tracers are used

  1. When a labeled chemical compound undergoes chemical reactions one or more of the products will contain the radioactive label. Analysis of what happens to the radioactive isotope provides detailed information on the mechanism of the chemical reaction.
  2. A radioactive compound is introduced into a living organism and the radio-isotope provides a means to construct an image showing the way in which that compound and its reaction products are distributed around the organism.


The commonly used radioisotopes have short half lives and so do not occur in nature in large amounts. They are produced by nuclear reactions. One of the most important processes is absorption of a neutron by an atomic nucleus, in which the mass number of the element concerned increases by 1 for each neutron absorbed. For example,

13C + n14C

In this case the atomic mass increases, but the element is unchanged. In other cases the product nucleus is unstable and decays, typically emitting protons, electrons (beta particle) or alpha particles. When a nucleus loses a proton the atomic number decreases by 1. For example,

32S + n32P + p

Neutron irradiation is performed in a nuclear reactor. The other main method used to synthesize radioisotopes is proton bombardment. The proton are accelerated to high energy either in a cyclotron or a linear accelerator.[3]

Tracer isotopes


Tritium (hydrogen-3) is produced by neutron irradiation of 6Li:

6Li + n4He + 3H

Tritium has a half-life 4500±8 days (approximately 12.32 years)[4] and it decays by beta decay. The electrons produced have an average energy of 5.7 keV. Because the emitted electrons have relatively low energy, the detection efficiency by scintillation counting is rather low. However, hydrogen atoms are present in all organic compounds, so tritium is frequently used as a tracer in biochemical studies.


11C decays by positron emission with a half-life of ca. 20 min. 11C is one of the isotopes often used in positron emission tomography.[3]

14C decays by beta decay, with a half-life of 5730 years. It is continuously produced in the upper atmosphere of the earth, so it occurs at a trace level in the environment. However, it is not practical to use naturally-occurring 14C for tracer studies. Instead it is made by neutron irradiation of the isotope 13C which occurs naturally in carbon at about the 1.1% level. 14C has been used extensively to trace the progress of organic molecules through metabolic pathways.[5]


13N decays by positron emission with a half-life of 9.97 min. It is produced by the nuclear reaction

1H + 16O13N + 4He

13N is used in positron emission tomography (PET scan).


15O decays by positron emission with a half-life of 122 sec. It is used in positron emission tomography.


18F decays predominately by β emission, with a half-life of 109.8 min. It is made by proton bombardment of 18O in a cyclotron or linear particle accelerator. It is an important isotope in the radiopharmaceutical industry. For example, it is used to make labeled fluorodeoxyglucose (FDG) for application in PET scans.[3]


32P is made by neutron bombardment of 32S

32S + n32P + p

It decays by beta decay with a half-life of 14.29 days. It is commonly used to study protein phosphorylation by kinases in biochemistry.

33P is made in relatively low yield by neutron bombardment of 31P. It is also a beta-emitter, with a half-life of 25.4 days. Though more expensive than 32P, the emitted electrons are less energetic, permitting better resolution in, for example, DNA sequencing.

Both isotopes are useful for labeling nucleotides and other species that contain a phosphate group.


35S is made by neutron bombardment of 35Cl

35Cl + n35S + p

It decays by beta-decay with a half-life of 87.51 days. It is used to label the sulfur-containing amino-acids methionine and cysteine. When a sulfur atom replaces an oxygen atom in a phosphate group on a nucleotide a thiophosphate is produced, so 35S can also be used to trace a phosphate group.


Main page: Physics:Technetium-99m

99mTc is a very versatile radioisotope, and is the most commonly used radioisotope tracer in medicine. It is easy to produce in a technetium-99m generator, by decay of 99Mo.

99Mo → 99mTc + e + νe

The molybdenum isotope has a half-life of approximately 66 hours (2.75 days), so the generator has a useful life of about two weeks. Most commercial 99mTc generators use column chromatography, in which 99Mo in the form of molybdate, MoO42− is adsorbed onto acid alumina (Al2O3). When the 99Mo decays it forms pertechnetate TcO4, which because of its single charge is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized 99Mo elutes the soluble 99mTc, resulting in a saline solution containing the 99mTc as the dissolved sodium salt of the pertechnetate. The pertechnetate is treated with a reducing agent such as Sn2+ and a ligand. Different ligands form coordination complexes which give the technetium enhanced affinity for particular sites in the human body.

99mTc decays by gamma emission, with a half-life: 6.01 hours. The short half-life ensures that the body-concentration of the radioisotope falls effectively to zero in a few days.


Main page: Physics:Isotopes of iodine

123I is produced by proton irradiation of 124Xe. The caesium isotope produced is unstable and decays to 123I. The isotope is usually supplied as the iodide and hypoiodate in dilute sodium hydroxide solution, at high isotopic purity.[6] 123I has also been produced at Oak Ridge National Laboratories by proton bombardment of 123Te.[7]

123I decays by electron capture with a half-life of 13.22 hours. The emitted 159 keV gamma ray is used in single-photon emission computed tomography (SPECT). A 127 keV gamma ray is also emitted.

125I is frequently used in radioimmunoassays because of its relatively long half-life (59 days) and ability to be detected with high sensitivity by gamma counters.[8]

129I is present in the environment as a result of the testing of nuclear weapons in the atmosphere. It was also produced in the Chernobyl and Fukushima disasters. 129I decays with a half-life of 15.7 million years, with low-energy beta and gamma emissions. It is not used as a tracer, though its presence in living organisms, including human beings, can be characterized by measurement of the gamma rays.

Other isotopes

Main page: Biology:Radiopharmacology

Many other isotopes have been used in specialized radiopharmacological studies. The most widely used is 67Ga for gallium scans. 67Ga is used because, like 99mTc, it is a gamma-ray emitter and various ligands can be attached to the Ga3+ ion, forming a coordination complex which may have selective affinity for particular sites in the human body.

An extensive list of radioactive tracers used in hydraulic fracturing can be found below.


In metabolism research, tritium and 14C-labeled glucose are commonly used in glucose clamps to measure rates of glucose uptake, fatty acid synthesis, and other metabolic processes.[9] While radioactive tracers are sometimes still used in human studies, stable isotope tracers such as 13C are more commonly used in current human clamp studies. Radioactive tracers are also used to study lipoprotein metabolism in humans and experimental animals.[10]

In medicine, tracers are applied in a number of tests, such as 99mTc in autoradiography and nuclear medicine, including single-photon emission computed tomography (SPECT), positron emission tomography (PET) and scintigraphy. The urea breath test for helicobacter pylori commonly used a dose of 14C labeled urea to detect h. pylori infection. If the labeled urea was metabolized by h. pylori in the stomach, the patient's breath would contain labeled carbon dioxide. In recent years, the use of substances enriched in the non-radioactive isotope 13C has become the preferred method, avoiding patient exposure to radioactivity.[11]

In hydraulic fracturing, radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of created fractures.[2] Tracers with different half-lives are used for each stage of hydraulic fracturing. In the United States amounts per injection of radionuclide are listed in the US Nuclear Regulatory Commission (NRC) guidelines.[12] According to the NRC, some of the most commonly used tracers include antimony-124, bromine-82, iodine-125, iodine-131, iridium-192, and scandium-46.[12] A 2003 publication by the International Atomic Energy Agency confirms the frequent use of most of the tracers above, and says that manganese-56, sodium-24, technetium-99m, silver-110m, argon-41, and xenon-133 are also used extensively because they are easily identified and measured.[13]


  1. "An introduction to the use of tracers in nutrition and metabolism". The Proceedings of the Nutrition Society 58 (4): 935–44. November 1999. doi:10.1017/S002966519900124X. PMID 10817161. 
  2. 2.0 2.1 Reis, John C. (1976). Environmental Control in Petroleum Engineering. Gulf Professional Publishers.
  3. 3.0 3.1 3.2 Fowler J. S. and Wolf A. P. (1982) The synthesis of carbon-11, fluorine-18 and nitrogen-13 labeled radiotracers for biomedical applications. Nucl. Sci. Ser. Natl Acad. Sci. Natl Res. Council Monogr. 1982.
  4. "Comprehensive Review and Critical Evaluation of the Half-Life of Tritium". Journal of Research of the National Institute of Standards and Technology 105 (4): 541–9. 2000. doi:10.6028/jres.105.043. PMID 27551621. PMC 4877155. 
  5. "Calculating radiation exposures during use of (14)C-labeled nutrients, food components, and biopharmaceuticals to quantify metabolic behavior in humans". Journal of Agricultural and Food Chemistry 58 (8): 4632–7. April 2010. doi:10.1021/jf100113c. PMID 20349979. 
  6. I-123 fact sheet[yes|permanent dead link|dead link}}]
  7. "Production of iodine-123 for medical applications". The International Journal of Applied Radiation and Isotopes 19 (4): 345–51. April 1968. doi:10.1016/0020-708X(68)90178-6. PMID 5650883. 
  8. "125-Iodine tracers for steroid radioimmunoassay". The Journal of Endocrinology 58 (1): xx. July 1973. PMID 4578967. 
  9. "Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues". Hormone and Metabolic Research. Supplement Series 24: 41–8. 1990. PMID 2272625. 
  10. "Measuring very low density lipoprotein-triglyceride kinetics in man in vivo: how different the various methods really are". Current Opinion in Clinical Nutrition and Metabolic Care 7 (5): 547–55. September 2004. doi:10.1097/00075197-200409000-00007. PMID 15295275. 
  11. "Urea breath test: a diagnostic tool in the management of Helicobacter pylori-related gastrointestinal diseases". Acta Gastro-Enterologica Belgica 61 (3): 332–5. 1998. PMID 9795467. 
  12. 12.0 12.1 "Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Well Logging, Tracer, and Field Flood Study Licenses (NUREG-1556, Volume 14)". US Nuclear Regulatory Commission. June 2000. "labeled Frac Sand...Sc-46, Br-82, Ag-110m, Sb-124, Ir-192" 
  13. Radiation Protection and the Management of Radioactive Waste in the Oil and Gas Industry (Report). International Atomic Energy Agency. 2003. pp. 39–40. Retrieved 20 May 2012. "Beta emitters, including 3H and 14C, may be used when it is feasible to use sampling techniques to detect the presence of the radiotracer, or when changes in activity concentration can be used as indicators of the properties of interest in the system. Gamma emitters, such as 46Sc, 140La, 56Mn, 24Na, 124Sb, 192Ir, 99Tcm, 131I, 110Agm, 41Ar and 133Xe are used extensively because of the ease with which they can be identified and measured. ... In order to aid the detection of any spillage of solutions of the 'soft' beta emitters, they are sometimes spiked with a short half-life gamma emitter such as 82Br..." 

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